Patients with borderline personality disorder and rejection-sensitive dysphoria participated in a program of clinical and biological evaluation. In addition to labile moods and behavioral dyscontrol, a high incidence of discrete major depressive episodes has been observed. Signs of neurophysiological dysfunction included a high incidence of psychomotor-psychosensory symptoms and a high incidence of neurological soft signs. Neuropsychological testing revealed a pattern of poor performance in tests of tonal memory, a function usually linked to the right temporal lobe. Procaine infusions frequently produced dysphorias similar to those occurring naturally, but generally produced only physiological symptoms in normal controls. Procaine activated a high frequency band of EEG activity over the temporal lobes in association with the dysphorias. Naloxone infusions being performed to investigate alteration in pain mechanisms. Methylphenidate infusions resulted in production of dysphorias similar to those occurring naturally but caused cardiac arrhythmias and have been discontinued.